Nonresponse to Ketamine in Treatment‐Resistant Bipolar Depression
Zofia Kachlik, Wiesław Jerzy Cubała, Michał Walaszek, Michał Pastuszak, Krzysztof Pastuszak, Aleksander Kwaśny
Neuropsychopharmacology Reports July 20, 2025 Peer reviewed DOI: 10.1002/npr2.70038 via OpenAlex
Summary
In a study of 35 patients with treatment-resistant bipolar depression (TRBD) receiving ketamine, 40% were nonresponders. Nonresponders had a higher median number of psychiatric comorbidities (2 compared to 1) and greater prior benzodiazepine use (64.3% vs. 23.8%). No significant associations were found between specific comorbidities or baseline suicidality and response to treatment. Ketamine was generally safe and well-tolerated despite these factors.
Study at a glance
| Design | post hoc analysis |
|---|---|
| Sample size | 35 |
| Population | patients with treatment-resistant bipolar depression |
| Key finding | Nonresponders to ketamine in TRBD had more psychiatric comorbidities and higher prior benzodiazepine use. |
Abstract
OBJECTIVES: Ketamine is a prototypical rapid-acting antidepressant for treatment-resistant bipolar depression (TRBD), yet many patients do not achieve a meaningful response. This study explored features of ketamine nonresponse in TRBD. METHODS: In a post hoc analysis of a naturalistic study, 35 TRBD patients received a four-week ketamine regimen (intravenous 0.5 mg/kg or oral 2.0/2.5 mg/kg). Response was measured using the Montgomery-Åsberg Depression Rating Scale, and baseline sociodemographic and clinical features were compared between responders and nonresponders. RESULTS: Fourteen patients (40%) were nonresponders. They had a higher median number of psychiatric comorbidities (2 vs. 1; p = 0.0366), were more likely to have any psychiatric comorbidity (78.6% vs. 33.3%; p = 0.0153), and had greater prior benzodiazepine use (64.3% vs. 23.8%; p = 0.0332). No significant links emerged between individual comorbidities or baseline suicidality and response. CONCLUSION: Ketamine demonstrates a favorable safety and tolerability profile for short time use in TRBD regardless of isolated baseline characteristics, although a more severe comorbidity burden and benzodiazepine use appear to be associated with nonresponse. TRIAL REGISTRATION: NCT04226963 and NCT05565352.